At higher dosages, it is used to treat opioid addiction in opioid-dependent individuals. In lower dosages it is used to control moderate-acute pain in non-opioid-tolerant individuals and in even lower dosages it is used to control moderate chronic pain.

Chemistry

Buprenorphine is a semi-synthetic morphinan derivative of the opioid alkaloid thebaine. Like many opioids, such as codeine or hydrocodone, it is has a morphinan backbone.

Buprenorphine and other molecules of this class contain a polycyclic core of three benzene rings fused in a zig-zag pattern called phenanthrene. A fourth nitrogen containing ring is fused to the phenanthrene at R9 and R13. Buprenophine (along with other morphinans) contains an ether bridge between two of its rings, connecting the benzene and opposite cyclohexane ring through an oxygen group.

Buprenorphine is unique to human medical opioids as it contains an addition fused ring which connects to the lower cyclohexane ring at R6 and R14. This structure is called a endoethenotetrahydrooripavine backbone, often found in veterinarian opioids. It contains a hydroxy group (OH-) substituted on the benzene ring and a methoxy group bound to the lower cyclohexane ring. The backbone of buprenorphine is also substituted with a methyl cyclopropyl moeity on its amino group. Adjacent to its methoxy attachment, the cyclohexane ring is bonded to R2 of a 2-butanol chain.

Pharmacology

Buprenorphine acts as a partial agonist of the μ-opioid receptor with a binding affinity of K~i~ = 1.5 nM; it also acts as an antagonist of the κ-opioid receptor with a binding affinity of K~i~ = 2.5 nM and the δ-opioid receptor with a binding affinity of K~i~ = 6.1 nM.

Buprenorphine exerts its effects by binding to and activating the μ-opioidreceptor. This occurs because opioids structurally mimic endogenous endorphins which are naturally found within the body and also work upon the μ-opioid receptor set. The way in which opioids structurally mimic these natural endorphins results in their euphoria, pain relief and anxiolytic effects. This is because endorphins are responsible for reducing pain, causing sleepiness, and feelings of pleasure. They can be released in response to pain, strenuous exercise, orgasm, or general excitement.

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWikicontributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects

Physical euphoria - This particular substance can be considered as less intense in its physical euphoria when compared with that of morphine or diacetylmorphine (heroin) due to it being a partial agonist of the μ-opioid receptor. The sensation itself can be described as extreme feelings of intense physical comfort, warmth and bliss which spreads throughout the body.

Cognitive effects

The general head space of buprenorphine is described by many as one of euphoria, relaxation, anxiety suppression and pain relief.

Cognitive euphoria - This particular substance can be considered as less intense in its cognitive euphoria when compared with that of morphine or diacetylmorphine (heroin) due to it being a partial agonist of the μ-opioid receptor. It is still, however, capable of extreme intensity and overwhelming bliss at heavier dosages with a low tolerance. The sensation itself can be described as powerful and overwhelming feeling of emotional bliss, contentment, and happiness.

Toxicity and harm potential

Buprenorphine has a low toxicity relative to dose: the ceiling dose for buprenorphine is usually between 16mg and 32mg, and anything above this will not produce an increase in respiratory depression (the primary cause of death in opioid overdose is severe respiratory depression, leading to respiratory collapse). Thus increasing the dose of buprenorphine above this level will not continue to increase risk of death in a fashion similar to other μ-opioid receptor agonists. As with all opioids, long-term effects can vary but can include diminished libido, apathy and memory loss.

Buprenorphine is often sold under the brand name Suboxone, which also contains naloxone. Naloxone is not orally active except at higher doses, so when large amounts of Suboxone are taken, the naloxone takes effect and reverses the effects of the buprenorphine. This is done to deter abuse of Suboxone.

Tolerance and addiction potential

As with other opioids, the chronic use of buprenorphine can be considered moderately addictive with a high potential for abuse and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal symptoms may occur if a person suddenly stops their usage.

Tolerance to many of the effects of buprenorphine develops with prolonged and repeated use. The rate at which this occurs develops at different rates for different effects, with tolerance to the constipation-inducing effects developing particularly slowly for instance. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). Buprenorphine presents cross-tolerance with all other opioids, meaning that after the consumption of buprenorphine all opioids will have a reduced effect.

Precipitated withdrawal syndrome

Buprenorphine has the ability to precipitate withdrawal symptoms in opiate-dependent individuals. This is due to buprenorphine only being a partial agonist, which does not activate the receptor with the appreciable efficacy of a full agonist, as well as having a very high binding affinity for the μ-opioidreceptor (Ki = 1.5nM), displacing other agonists that may still be attached when the buprenorphine is ingested.

Note: It is a common misconception that naloxone, in some buprenorphine formulations, is what causes the precipitated withdrawal syndrome to manifest. This is false, as naloxone has a lower binding than Buprenorphine, as well as being inactive through most routes of administration.

Dangerous interactions

Although many drugs are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

Dissociatives - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If unconsciousness occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.

Stimulants - It is dangerous to combine buprenorphine, a depressant, with stimulants due to the risk of excessive intoxication. Stimulants decrease the sedative effect of buprenorphine, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of buprenorphine will be significantly increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to only taking a certain amount of buprenorphine.

Legality

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European Union - Buprenorphine can be used either alone or in combination with another substance and is approved for the treatment of opioid addiction.[2]

Netherlands - Buprenorphine a List II drug of the Opium Law, although special rules apply to its prescription and dispensation.[citation needed]

United States - Buprenorphine, either alone or in combination with naloxone (as, for example, Suboxone), is a Schedule III drug.

Prior to the approval of Suboxone in the U.S. for treating opioid addiction, the Drug Addiction Treatment Act of 2000 was passed. This law gives the Secretary of Health and Human Services the authority to grant a waiver to all physicians with appropriate training to prescribe and administer narcotics from Schedules III-V in the treatment of drug addiction. Prior to the passage of this law such authority was restricted solely to physicians working in an outpatient clinic specifically designed for treatment of addiction.[3] The waiver, which requires the physician to undergo an 8-hour training course, initially allowed that physician to treat only 10 patients in this manner; as of 2016, this limit has been increased to 275.[4]

Canada - Buprenorphine is a schedule I substance in Canada and is only available with a valid prescription. [5]